In conformity with our overall goals of uncovering specific means to alter the expression of the transformed genome of mammary epithelial cells, whether they be preneoplastic or neoplastic, we have studied mammary tissues at three levels. In the intact animal, we have shown that the rat mammary adenocarcinoma R3230AC will respond to the hormones of lactation by an increase in its lipogenic capacity. Thus, in contrast to the mammary tumors in C3H mice, these rat tumors are hormonally responsive. In addition, we have established that in the mouse, mammary tumor growth could be depressed by fat-free or saturated fat diets and is enhanced by dietary linoleate. Dietary Eicosa-5,8,11,14-tetraynoic acid (TYA) was effective in preventing the conversion of linoleate to arachidonate by the intact mouse and also inhibited tumor growth. Thus, our evidence suggests that the growth rate is related to the arachidonate content rather than the linoleate content of the tumors. The involvement of prostaglandins in this process is under further investigation. On the cellular level, we have made some progress toward developing specific culture conditions that allow maximal synthesis of the products characteristic of the totally differentiated mouse mammary epithelial cells. To this end, the relationship between the interaction of different cell types when maintained in culture is being investigated on the basis of enzyme activities and metabolic throughput. Our studies with isolated mammary epithelial cell fractions are directed toward the study of the surface changes which occur during the transition from a normal to a neoplastic phenotype. We have demonstrated that the presence of 5'-nucleotidase in the surface membrane can be used to monitor modulation of gene expression in the murine adenocarcinoma. In the future, we will use this enzyme as well as other markers, such as the binding of specific cell surface antibodies which we have developed, to monitor chemical and structural changes coexistent with modulation of genome expression. BIBLIOGRAPHIC REFERENCES: "Effect of Maternal Diet on Fetal Hepatic Lipogenesis," S.G. Miguel and S. Abraham, Biochim. Biophys. Acta 424:213-234, 1976. "Enhanced Growth Rate of Transplanted Mammary Adenocarcinoma Induced in C3H Mice by Dietary Linoleate," G. Ananda Rao and S. Abraham, J. Nat. Cancer Inst. 56:431-432, 1976.